Oncology Research最新文献

{"title":"Multi-Omics Identification of UBE2C as a Prognostic Biomarker and Therapeutic Target Linked to Topotecan Sensitivity in Cervical Cancer.","authors":"Emmanuel Naveen Raj, Chia-Jung Li, Shih-Hsuan Cheng, Su-Boon Yong, Zhi-Hong Wen, An-Jen Chiang","doi":"10.32604/or.2026.079551","DOIUrl":"10.32604/or.2026.079551","url":null,"abstract":"<p><p><b>Objectives</b>: Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) necessitate the discovery of novel biomarkers for prognostic and therapeutic advancement. This study aims to evaluate the clinical significance of ubiquitin-conjugating enzyme E2C (UBE2C) and its association with the tumor microenvironment (TME) in CESC. <b>Methods</b>: We meticulously sourced CESC data from renowned repositories such as The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO), leveraging cutting-edge techniques including single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and pharmacogenomics. Through multifaceted data analysis, we endeavored to unravel the intricate role and potential value of UBE2C in CESC tumorigenesis and progression. <b>Results</b>: Analysis of public datasets confirms UBE2C elevation in CESC tumors, correlating with advanced stages, metastasis, and poor disease-free survival (DFS). Dependency screens and functional enrichment highlight UBE2C's critical role in cell viability and DNA replication. Notably, multi-omics and spatial transcriptomics reveal a strong link between UBE2C expression and macrophage infiltration (CD63⁺) in tumor regions. Finally, pharmacogenomic profiling and molecular docking identified Topotecan as a potent therapeutic agent with high UBE2C binding affinity. <b>Conclusion</b>: In conclusion, UBE2C expression is associated with cervical cancer progression and correlates with an immunosuppressive macrophage-enriched microenvironment, making it a promising candidate for further investigation in therapeutic intervention.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 9","pages":"18"},"PeriodicalIF":4.6,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction: Long Noncoding RNA MEG3 Suppresses Glioma Cell Proliferation, Migration, and Invasion by Acting as a Competing Endogenous RNA of miR-19a.","authors":"","doi":"10.32604/or.2026.090478","DOIUrl":"https://doi.org/10.32604/or.2026.090478","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.3727/096504017X14886689179993.].</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 9","pages":"29"},"PeriodicalIF":4.6,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumour-Derived sEVs Promote Triple-Negative Breast Cancer Progression Associated with HAVCR2 Upregulation in Macrophages.","authors":"Jia Liu, Binqian Wang, Yannan Jin, Wenquan Chen, Ruohan Shi, Weijia Wang, Xiaojing Zhang, Yi Tan, Zhongran Man, Bo Hu, Lisen Zhu, Biao Zhang, Chongchan Bao, Gongsheng Jin","doi":"10.32604/or.2026.079137","DOIUrl":"10.32604/or.2026.079137","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Backgrounds:&lt;/b&gt; Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with a unique tumor microenvironment, and while Programmed cell death protein 1/Programmed cell death ligand 1 (PD-1/PD-L1) blockade represents a standard immunotherapy, most patients develop primary or acquired resistance, with few alternative immunotherapeutic targets currently available. Therefore, we aimed to identify potential immune checkpoint-related molecules involved in TNBC-macrophage crosstalk, clarify the underlying molecular mechanism mediated by small extracellular vesicles (sEVs), and provide a theoretical basis for the future development of novel immunotherapeutic targets against TNBC. &lt;b&gt;Methods:&lt;/b&gt; Single-cell RNA-sequencing (scRNA-seq) datasets for various breast cancer subtypes were used. Pseudotime trajectory, cell‒cell communication and Tumor Immune Estimation Resource 2.0 (TIMER2) analyses were conducted to characterize the tumour microenvironment (TME). Immunochemistry and immunofluorescence were used to confirm the results of the above analyses. Single-nucleus RNA sequencing (snRNA-seq) was conducted on three pairs of TNBC tumour and adjacent normal tissues. The functions of tumour-associated macrophages (TAMs) and sEVs in TNBC metastasis were explored by Western blotting, flow cytometry and cell-based experiments. &lt;b&gt;Results:&lt;/b&gt; A total of nearly 60,000 high-quality single cells were subjected to scRNA-seq analysis, from which seven major cell types were identified. An overall increase in immune cell proportion was observed in TNBC compared with other subtypes, with the immune cell fraction in TNBC tissues being ~1.8-fold higher than that in luminal A/HER2+ subtypes (&lt;i&gt;p&lt;/i&gt; &lt; 0.001). Cell‒cell communication analysis indicated that TNBC cells mainly interact with macrophages. Interestingly, HAVCR2, an immune checkpoint, is expressed mainly in macrophages in the TNBC TME. HAVCR2 is associated with macrophage pseudotime progression in TNBC, which was validated by immunofluorescence staining. Moreover, analysis of The Cancer Genome Atlas (TCGA) bulk RNA-seq data revealed that HAVCR2 expression is significantly correlated with M2-like macrophage gene signatures and computationally inferred macrophage infiltration levels in TNBC, and this tissue-level transcriptional correlation is associated with poor patient prognosis. Notably, bulk RNA-seq data cannot define discrete cell subsets, and the identification of HAVCR2+ M2 macrophage subsets was independently validated by scRNA-seq and snRNA-seq at the single-cell level. Furthermore, treatment with TNBC-derived sEVs is associated with concurrent increases in the expression of HAVCR2 and M2-associated markers (CD163, CD206) in macrophages. These findings reflect a correlative association rather than a demonstrated causal or regulatory relationship between HAVCR2 and M2-associated marker upregulation. &lt;b&gt;Conclusion:&lt;/b&gt; sEVs derived from TNBC cells are associated with the","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 8","pages":"19"},"PeriodicalIF":4.6,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual Regulatory Functions and Therapeutic Potential of CD48 in Tumor Immunity.","authors":"Zhenan Lin, Zhongwu Chen, Zihua Deng, Tingting Bao, Sandi Shen","doi":"10.32604/or.2026.082272","DOIUrl":"10.32604/or.2026.082272","url":null,"abstract":"<p><p>Cluster of differentiation 48 (CD48) is a glycosylphosphatidylinositol-anchored member of the signaling lymphocyte activation molecule (SLAM) family that is predominantly expressed on hematopoietic cells and regulates immune-cell communication through 2B4 (CD244) and CD2. This narrative review critically summarizes the context-dependent role of CD48 in tumor immunity, with emphasis on the distinction between activating trans-interactions and potentially inhibitory cis-interactions. Evidence from hematologic malignancies and selected solid tumors indicates that CD48 may support antitumor immunity by facilitating natural killer (NK) cells activation, CD8⁺ T-cell co-stimulation, immune synapse formation, and effector cytokine production. Conversely, loss of CD48 expression, sustained CD48-2B4 engagement, altered ligand density, and suppressive myeloid-rich tumor microenvironment (TME) may contribute to immune escape or NK cells dysfunction. Current therapeutic concepts, including anti-CD48 monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, engineered NK/T cells, and epigenetic restoration of CD48 expression, remain largely preclinical and require cautious interpretation. Major translational barriers include broad CD48 expression on normal hematopoietic populations, soluble CD48 (sCD48) interference, uncertain biomarker standardization, and the risk that forced activation in dense solid tumors may reinforce cis-inhibitory signaling rather than improve cytotoxicity. Future studies should define tumor-type-specific signaling states, quantify sCD48, integrate spatial and single-cell approaches, and evaluate rational combinations with programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade in mechanism-driven models before clinical translation. This review aims to critically evaluate the dual regulatory roles of CD48 in tumor immunity, distinguish between activating trans-interactions and potentially inhibitory cis-interactions across different tumor types, and assess the translational potential and challenges of CD48-targeted immunotherapeutic strategies.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 8","pages":"11"},"PeriodicalIF":4.6,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crosstalk between Extracellular Vesicles and the Tumor Microenvironment: Mechanistic Insights and Therapeutic Opportunities.","authors":"Yaqi Xu, Jia Zhao, Xiaowen Mao","doi":"10.32604/or.2026.079562","DOIUrl":"10.32604/or.2026.079562","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are actively secreted, membrane-enclosed nanoparticles that serve as pivotal mediators of intercellular communication. They function as key mediators of intercellular communication by transporting diverse biomolecules, including proteins, nucleic acids, and metabolites. Within the tumor microenvironment, EVs drive complex cellular crosstalk and critically regulate tumor progression by remodeling the extracellular matrix, conferring drug resistance, and reprogramming immune responses. Given their natural biocompatibility, tissue tropism, and ability to cross biological barriers, EVs have emerged as promising platforms for immunotherapy, tumor vaccines and targeted drug delivery system. Moreover, the rapid expansion of EV-based clinical trials highlights their promise in precision medicine. Concurrently, the limitations associated with EV-based therapeutic strategies are critically evaluated to inform future development. This review has also detailed the importance of single-vesicle analysis, which represents a rapidly evolving frontier in EV science. Aiming to bridge the gap between mechanistic understanding and clinical practice, this review delineates the pivotal roles of EV-mediated communication in reshaping the dynamic homeostasis of the tumor microenvironment. Moreover, we provide a critical analysis of current EV-based therapeutic pipelines and their translational challenges, offering key perspectives and theoretical support for the future of precision medicine.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 8","pages":"7"},"PeriodicalIF":4.6,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunohistochemical Expression of Novel Therapeutic Targets in Squamous Cell Carcinoma of the Bladder.","authors":"Lisa J Frey, Nina Lache, Nikita D Fischer, Niklas Rölz, Lisa Frey, Maximilian Haack, Gregor Duwe, Stefan Porubsky, Axel Haferkamp, Daniel-C Wagner, Maximilian P Brandt","doi":"10.32604/or.2026.078954","DOIUrl":"10.32604/or.2026.078954","url":null,"abstract":"<p><strong>Objectives: </strong>Squamous cell carcinoma (SCC) of the bladder is an aggressive histologic subtype with distinct clinical behavior and limited treatment options after platinum-based chemotherapy. This study aimed to evaluate potential therapeutic targets in bladder SCC.</p><p><strong>Methods: </strong>A retrospective cohort of 790 patients who underwent radical cystectomy for bladder cancer between 2011 and 2021 was screened to identify cases with histologically confirmed SCC. All SCC cases in the pathology department from 2003 to 2011 were also reviewed. Clinical and pathological data from 54 patients were analyzed. A tissue microarray (TMA) was constructed, and immunohistochemical (IHC) analyses were performed for programmed death-ligand 1 (PD-L1), nectin cell adhesion molecule 4 (NECTIN4), trophoblast cell-surface antigen 2 (TROP2), human epidermal growth factor receptor 2 (HER2), carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), and CD8⁺ T cells. Expression levels were assessed for prognostic relevance using the log-rank test and Kaplan-Meier survival analysis.</p><p><strong>Results: </strong>A TMA comprising samples from 42 of 54 patients (22 pure SCC, 20 partial SCC) was successfully constructed. NECTIN4 (positive vs. negative) expression, PD-L1 (combined positive score ≥ 10 vs. <10) expression, and CD8⁺ density (high vs. low) showed a nearly equal distribution across the cohort. HER2 expression was detected in 14.3% of cases, CEACAM5 in 21.4%, and TROP2 in 83.3% of tumors. High NECTIN4 expression, increased CD8⁺ density, and administration of adjuvant chemotherapy were associated with improved overall survival.</p><p><strong>Conclusion: </strong>Several actionable targets were identified in bladder SCC, supporting further exploration of targeted therapies.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 8","pages":"14"},"PeriodicalIF":4.6,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Aurora A Kinase Enhance the CDK4/6 Inhibitor Sensitivity in HR+/HER2- Breast Cancer.","authors":"Juan Wu, Yue Wang, Honglin Yan, Juanjuan Li, Chuntao Quan, Jingping Yuan, Shengrong Sun","doi":"10.32604/or.2026.081653","DOIUrl":"10.32604/or.2026.081653","url":null,"abstract":"<p><strong>Objectives: </strong>Despite the success of CDK4/6 inhibitors (CDK4/6i) in treating HR+/HER2- breast cancer (BC), some patients experience treatment failure due to CDK4/6i resistance. This study aimed to investigate whether targeting Aurora A kinase enhances CDK4/6 inhibitor sensitivity.</p><p><strong>Methods: </strong>An Abemaciclib-resistant cell line (MCF7AR) was developed by treating MCF7 cells with gradually increasing concentrations of Abemaciclib. We evaluated the relative protein levels of p-RB, p-Aurora A, Aurora A, and USP22 in cell cultures, animal tissues, and clinical samples. The effect of Aurora A inhibition on reversing CDK4/6i resistance was assessed using cell viability assays and tumor xenograft experiments. We examined the relationship between Aurora A kinase activation levels and resistance to CDK4/6i.</p><p><strong>Results: </strong>CDK4/6i-resistant cell lines and patient samples exhibited elevated levels of phosphorylated Aurora A and retinoblastoma protein (RB). Previous studies have reported that RB inactivation can activate the spindle assembly checkpoint (SAC), leading to mitotic delay. High Aurora A activity counteracts the SAC-induced delay, thereby promoting mitosis. CDK4/6i treatment increased Aurora A protein levels through regulation by USP22, enhancing Aurora A activity and overcoming SAC-mediated cell cycle arrest. Combined therapy with Aurora A inhibitor (Aurora Ai) and CDK4/6i demonstrated synergistic antitumor effects both <i>in vitro</i> and <i>in vivo</i>. Clinical data suggest that HR+/HER2- patients with high levels of phosphorylated RB and Aurora A may exhibit resistance to CDK4/6i.</p><p><strong>Conclusion: </strong>Aurora A contributes to CDK4/6i resistance by overcoming SAC delay and promoting mitosis. In RB-inactivated CDK4/6i-resistant cells, Aurora A inhibition may induce a synthetic lethal effect.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 8","pages":"25"},"PeriodicalIF":4.6,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GPX4 Defines an Immune-Cold Phenotype and Poor Prognosis in Resected Lung Adenocarcinoma.","authors":"Ganxin Wang, Zhongan Liu, Tian Zhou, Boting Yang, Jiaqin Chen, Jing Chen, Kai Huang, Yunqing Xu, Quan Tang, Xiangqian Yin, Guangqin Xiao, Sijia Zhang","doi":"10.32604/or.2026.083840","DOIUrl":"10.32604/or.2026.083840","url":null,"abstract":"<p><p><b>Objectives:</b> Ferroptosis resistance may contribute to tumor progression and immune escape. This study evaluated the prognostic and immunological significance of glutathione peroxidase 4 (GPX4), a core ferroptosis-suppressive enzyme, in surgically resected lung adenocarcinoma. <b>Methods:</b> We retrospectively analyzed 104 patients with primary lung adenocarcinoma who underwent curative resection. GPX4 protein expression was assessed by immunohistochemistry (IHC) using the histological score (H-score), and patients were classified as GPX4-low (n = 54) or GPX4-high (n = 50). Intratumoral immune contexture was quantified using CD3, CD4, CD8, CD68, programmed cell death protein 1 (PD-1), and programmed death-ligand 1 (PD-L1) staining. Disease-free survival (DFS) and overall survival (OS) were analyzed using Cox regression. Cutoff sensitivity analyses, category consolidation, ridge-penalized Cox regression, events-per-variable assessment, bootstrap internal validation, and interobserver reproducibility testing were performed to strengthen statistical robustness. <b>Results:</b> GPX4-high tumors were associated with systemic inflammatory and immune-related features, including elevated fibrinogen (<i>p</i> = 0.015), lower lymphocyte-to-monocyte ratio (<i>p</i> = 0.003), and altered aspartate aminotransferase-to-alanine aminotransferase ratio (<i>p</i> = 0.028). GPX4-high tumors showed reduced intratumoral CD3⁺, CD4⁺, CD8⁺, and CD68⁺ immune-cell infiltration, together with increased PD-1 and PD-L1 expression, indicating an immune-cold yet checkpoint-enriched phenotype. After category consolidation and ridge-penalized multivariable adjustment, high GPX4 expression remained independently associated with worse DFS (HR, 8.63; 95% CI, 2.99-24.91; <i>p</i> < 0.001) and OS (HR, 6.94; 95% CI, 2.44-19.74; <i>p</i> < 0.001). GPX4-based prognostic models showed bias-corrected C-index values of 0.782 for DFS and 0.826 for OS, with calibration slopes of 0.964 and 0.937, respectively. <b>Conclusions:</b> High GPX4 expression identifies a clinically adverse, ferroptosis-resistant, immune-remodeled phenotype in resected lung adenocarcinoma. Integrating GPX4 with clinicopathological and inflammatory variables may improve postoperative risk stratification.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 8","pages":"26"},"PeriodicalIF":4.6,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Navigating the Metabolic-Genomic Paradigm: Mitochondrial Reprogramming as a Driver of Cancer Plasticity.","authors":"Yen-Dun Tony Tzeng, Chen-Yueh Wen, Su-Boon Yong, Zhi-Hong Wen, An-Jen Chiang, Chia-Jung Li","doi":"10.32604/or.2026.078924","DOIUrl":"10.32604/or.2026.078924","url":null,"abstract":"<p><p>Breast cancer (BC) management has transitioned from histological classification to molecular subtyping, yet therapeutic resistance and intratumor heterogeneity remain critical clinical challenges. This review examines the emerging paradigm shift toward integrating mitochondrial metabolism into the precision medicine framework. We detail the complex mitonuclear crosstalk where nuclear genetic alterations, such as Breast Cancer 1 (<i>BRCA1</i>) deficiency and <i>TP53</i> mutations, fundamentally reprogram mitochondrial bioenergetics. Specifically, the loss of BRCA1 function triggers a systemic NAD⁺ depletion trap through <i>PARP1</i> hyperactivation, while oncogenic drivers like <i>MYC</i> coordinate with <i>PGC1α</i> to enhance mitochondrial biogenesis for metastatic survival. We evaluate the diagnostic potential of mitochondrial DNA heteroplasmy and machine learning derived metabolic gene signatures as high performance biomarkers for patient stratification and the detection of minimal residual disease via liquid biopsy. Furthermore, we analyze current clinical efforts to target mitochondrial vulnerabilities, including respiratory chain inhibitors like metformin and BH3 mimetics, while highlighting the significant challenges posed by metabolic plasticity and nutrient competition in the tumor microenvironment. The analysis of clinical trial data, such as the MA.32 study, suggests that metabolic interventions require precise patient selection based on specific metabolic phenotypes rather than broad application. Looking forward, the integration of genome scale metabolic models and artificial intelligence (AI) offers a transformative pathway to simulate patient specific metabolic fluxes and identify novel synthetic lethal targets. By bridging the gap between nuclear genomic drivers and dynamic mitochondrial adaptations, this review aims to provide a preliminary framework for the exploration of metabolic-genomic precision oncology in BC.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 8","pages":"5"},"PeriodicalIF":4.6,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Excellent Survival Outcome in a Patient Receiving NALIRIFOX for Metastatic Pancreatic Adenocarcinoma: A Case Report.","authors":"Abdullah Esmail, Waseem Abdelrahim, Ebtesam Al-Najjar, Raed Zaidan, Tahrir Abdelrahim","doi":"10.32604/or.2026.083192","DOIUrl":"10.32604/or.2026.083192","url":null,"abstract":"<p><p><b>Background:</b> Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy that is frequently diagnosed at an advanced stage and remains associated with poor survival outcomes. Durable responses to systemic therapy in metastatic disease are uncommon. We report a case of metastatic PDAC with prolonged survival and sustained response following first-line treatment with NALIRIFOX. This report describes a patient with metastatic PDAC who achieved prolonged disease control and sustained response following first-line treatment with NALIRIFOX. <b>Case Presentation:</b> A 64-year-old woman presented with abdominal pain, early satiety, weight loss, and markedly elevated CA 19-9 levels. Imaging demonstrated a pancreatic head mass with multiple hepatic metastases, and biopsy confirmed metastatic poorly differentiated PDAC. The patient initiated first-line therapy with NALIRIFOX as part of the NAPOLI-3 protocol and completed 20 cycles over approximately 25 months. Following an early treatment delay secondary to grade 2 neutropenia, she achieved substantial biochemical and radiographic improvement. After eight cycles, imaging demonstrated marked radiographic response with disappearance of the pancreatic lesion and marked regression of hepatic metastases. Disease stability was maintained for more than two years before progression was identified in a dominant hepatic lesion after cycle 20. <b>Conclusion:</b> This case highlights the potential for prolonged disease control and extended survival with NALIRIFOX in metastatic PDAC, emphasizing the meaningful clinical benefit that may be achieved in selected patients despite historically poor outcomes.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 8","pages":"28"},"PeriodicalIF":4.6,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}